title: Traditional Chinese medicine for the treatment of primary dysmenorrhea: how do Yuanhu painkillers effectively treat dysmenorrhea?
abstract: OBJECTIVE
  To examine the efficacy of YuanHu painkillers (YHP) as a treatment for primary dysmenorrhea and to reveal YHP's principle formula.
  
  
  METHODS
  A Wistar rat uterine contraction model was utilized in this study. Rats were given 0.698g/kg YHP, 0.07g/kg tetrahydropalmatine (THP; YHP's main component), 0.02g/kg imperatorin (IMP), or THP+IMP (0.07+0.02g/kg) as polypharmacy (PG) by gavage. H&E staining and histopathological examination of the uteri tissue samples were performed. We then detected superoxide dismutase (SOD) and malondialdehyde (MDA), nitric oxide (NO), as well as inducible nitric oxide synthase (iNOS), i-κB, nuclear factor-κB (NF-κB), and cyclooxygenase-2 (COX-2) indices.
  
  
  RESULTS
  PG significantly inhibited the uterine contraction of the primary dysmenorrhea rat model (p<0.05), and was significantly different than single-agent therapy (p<0.05). Histopathological examination showed inflammation in the uteri of the control group which YHP and its main constitutes alleviated. THP significantly inhibited the contraction of isolated uteri caused by Ach, PGF2α and oxytocin in a concentration-dependent fashion. THP and IMP both significantly affected the levels of NO, activation of NF-κB, up-regulated the expression of i-κB and down-regulated the expression of both iNOS and COX-2. IMP obviously decreased the level of MDA and increased the activation of SOD (p<0.05). PG obviously improved all the parameters mentioned above (p<0.05).
  
  
  CONCLUSIONS
  YHP exerted protective effects on primary dysmenorrhea in rats and remarkably alleviated the severity of experimental primary dysmenorrhea. The combined strategy proved to be more effective than either THP or IMP alone and may have synergistic effects in combination in primary dysmenorrhea. Mechanisms that might account for the beneficial effects include abating oxidative stress, inhibiting over-inflammatory reaction, and alleviating the contraction of isolated rat uteri by inhibiting the influx of extracellular Ca(2+). Broad potential for future clinical practice is foreseeable.
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. xianyu.fansheng@163.com
authors.forename: Yuetao
authors.initials: Y
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Xie
authors.forename: Xiaokai
authors.initials: X
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Li
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Sun
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Qiu
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Siwang
authors.initials: S
authors.lastname: Wang
mesh_terms: D029971:Angelica sinensis; D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004412:Dysmenorrhea / Q000188:drug therapy*; D005260:Female; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D059408:Pain Management; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001600:Berberine Alkaloids; D004365:Drugs, Chinese Herbal; D011564:Furocoumarins; C014215:tetrahydropalmatine; C044613:angelicae sinensis extract; C031534:imperatorin
keywords: Ca(2+) channel; Imperatorin; NF-κB; Primary dysmenorrhea; Tetrahydropalmatine; YuanHu painkillers